The focus of the work is to develop new investigative imaging and biomechanical analysis techniques to better understand atherosclerosis and plaque behavior in humans. The early work has focused on development of improved MR imaging techniques for direct visualization of coronary disease inclusive of the wall. These have advanced both spatial and temporal resolution, improving the former by a factor of eight and the latter by a factor of five. Additionally, molecular imaging of plaque in animal models via an integrin targeted optical probe has served to inform biomechanical modeling of the atherosclerotic plaque. This allows the quantification of the relative roles of arterial wall necrotic core thickness, remodeling index and cap thickness in plaque rupture. As regards modeling the solid biomechanics of atheromatous plaque, our early work in this emerging field has shed new light on the previously held view of a plaque cap thickness of 65 microns as the threshold for vulnerability and plaque rupture, showing rupture- from a biomechanics standpoint- as a more complex interplay between the aforementioned triad of physical features (lipid core thickness, cap thickness, remodeling index) and that rupture, while more common below this cap thickness, is not so strictly dependent on it and can occur in early lesions at much greater cap thicknesses. One of the major challenges for the next generation of clinical imaging methods for risk assessment is that identification of vulnerable atheroma requires not only an accurate description of plaque morphology, but also a precise knowledge of biomechanical properties of plaque constituents. Indeed, such knowledge will likely allow a precise evaluation of the thin-cap fibro-atheroma peak stress amplitude, which is a reliable predictor of plaque rupture. Working toward this goal we developed a novel imaging technique (called iMOD) to extract from IVUS sequences the plaque morphology and Youngs modulus of each plaque component. In collaboration with our French colleagues, we successfully conducted vascular phantom experiments and demonstrated the feasibility of our new IVUS elasticity modulus imaging approach iMOD. Recently we published our first in vivo preliminary results showing the performance of our plaque elasticity reconstruction model iMOD to extract morphology and elasticity map from the IVUS sequence in twelve patients referred for a directional coronary atherectomy. If successful, this could provide a key missing link in the information needed to model individual plaques and assess rupture likelihood.